Abstract 1549TiP
Background
The inhibitory Notch ligand, delta-like ligand 3 (DLL3), is a compelling therapeutic target due to its aberrant expression on the cell surface in most small cell lung cancer (SCLC). Tarlatamab (AMG 757) is a half-life extended bispecific T-cell engager (HLE BiTE®) molecule designed to specifically bind DLL3 on target cancer cells and CD3 on T cells, resulting in T cell-dependent killing of tumor cells. Data from an ongoing first-in-human monotherapy study show acceptable safety with evidence of tarlatamab efficacy in patients with relapsed/refractory SCLC (NCT03319940). Adding programmed death ligand 1 (PD-L1) inhibitors to first-line platinum chemotherapy is the emerging standard-of-care (SOC) in ES-SCLC and preclinical data suggests increased antitumor activity of BiTE molecules when combined with PD-1/PD-L1 inhibition or chemotherapy.1 These data support a clinical trial of tarlatamab combined with frontline carboplatin, etoposide, and PD-L1 inhibition in ES-SCLC.
Trial design
This is a phase 1b, multicenter, open-label study evaluating tarlatamab in combination with first-line SOC chemo-immunotherapy in subjects with ES-SCLC. Tarlatamab will be evaluated in two separate settings: A) In combination with carboplatin, etoposide, and a PD-L1 inhibitor followed by maintenance cycles of tarlatamab plus PD-L1 inhibitor, and B) In combination with PD-L1 inhibitor following SOC chemo-immunotherapy as a maintenance only approach. Key eligibility criteria include patients with histologically or cytologically confirmed ES-SCLC with no prior systemic treatment (except as specified in protocol) and ECOG performance status ≤1. The primary objective is to evaluate the safety, tolerability, and determine the recommended phase 2 dose and/or maximum tolerated dose of tarlatamab in combination with PD-L1 inhibition with or without chemotherapy. Secondary endpoints are objective response rate, duration of response, disease control, progression-free survival, overall survival, and pharmacokinetics. References Belmontes B, et al. Sci. Transl. Med. 2021;13:eabd1524.
Clinical trial identification
NCT05361395.
Editorial acknowledgement
Medical writing support for this poster was provided by Eugene Gillespie, PhD, of Amgen, Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
S.M. Gadgeel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Genentech/Roche, Bristol Myers Squibb, Pfizer, Novartis, Blueprint, Daiichii; Financial Interests, Personal, Other, Data Safety Monitoring Board: AstraZeneca. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Takeda, Merck, MSD, Amgen, Yuhan, Daiichi-Sankyo, Roche, Pfizer, Arcus, Alpha-pharmaceuticals; Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, Takeda, Merck, MSD, Amgen, Yuhan, Daiichi-Sankyo, Roche, Pfizer. S-W. Kim: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Amgen; Financial Interests, Personal, Yuhan. Financial Interests, Personal, Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Norvasc, Takeda, Yuhan. L. Paz-Ares: Financial Interests, Personal, Advisory Board: Roche, MSD, Merck Serono, BMS, AZ, Lilly, Pfizer, PharmaMar, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Invited Speaker: Altum sequencing, Amgen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar. H. Prenen: Financial Interests, Institutional, Advisory Board: Amgen, Roche, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Bayer, Ipsen, Sanofi. M. Boyer: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Merck Sharpe & Dohme, Amgen, Janssen, Eli Lilly, EARLI, Immugene, Dizal; Non-Financial Interests, Leadership Role: Thoracic Oncology Group Australasia. B. Solomon: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer; Financial Interests, Institutional, Invited Speaker: Daiichi-Sankyo, Iovance, GSK, Mirati, ImmunityBio, AstraZeneca, Amgen; Non-Financial Interests, Member: ASCO, AACR, ESMO. S. Huang: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. M. Minocha: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. M. Kistler: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. N. Hashemi Sadraei: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. All other authors have declared no conflicts of interest.